Cholera is a waterborne disease that becomes explosive in some areas during periods of heavy rainfall. Attempts to understand these outbreaks have focused on connections between environmental reservoirs and climate variability. However, in addition to environment and climate, household transmission, human host, and pathogen genetic factors are known or suspected to play key roles in cholera transmission. Here, we hypothesize that the interplay of multiple environmental, human, and pathogen factors determine the dynamics of endemic versus epidemic cholera transmission in different geographic areas. To test this hypothesis, we will develop a mathematical model of cholera transmission to examine the relative roles of such factors. The applicant, David M. Hartley, PhD, is an Assistant Professor in the Department of Epidemiology and preventive Medicine at the University of Maryland School of Medicine. He is trained (BS, MS, PhD) as an applied physicist. The proposed training is intended to provide him with an MPH degree in the setting of a strong mentored research program. His goal is to extend recent research interests focused on emerging vectorborne infections and bioterrorism to more complex diseases, including those in which genetic data may ultimately be key to understanding population dynamics. In the proposed research, we will construct a dynamical spatial cholera model to examine emergence and spread within and between communities. Objectives are to (1) Analyze and elucidate the role of direct contact with V. cholerae in a hyper-infectious state versus indirect contact with V. cholerae in a less-infectious state within a locality. Rationale: Less-frequent contact with highly infectious agent may be as important as more-frequent contact with less infectious agent. (2) Elucidate the impact of dilution of V. cholerae released by infectious individuals into reservoirs of drinking water such as rivers. Rationale: V. cholerae prominence in water supplies, as a function of water volume and flow rates, is expected to affect human exposure in terms of dosage. (3) Investigate the question of why El Tor has displaced the classical biotype to become the dominant pandemic strain. Rationale: The dynamics of evolutionary advantage in terms of virulence is expected to determine cholera strain success. The long-term goal is to rigorously understand the global dynamics of cholera emergence, transmission, and persistence. Understanding these interactions may allow us to predict the onset and potentially the intensity of epidemics in endemic regions, as well as the speed and intensity of spread of cholera as it enters naive regions. Such an understanding may also afford us insight into new prevention, intervention and control strategies to limit or prevent the occurrence of this potentially devastating disease.